Pharmacological Efficacy of Tamarix aphylla - MDPI

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Citation: Alshehri, S.A.; Wahab, S.;

Abullais, S.S.; Das, G.; Hani, U.;

Ahmad, W.; Amir, M.; Ahmad, A.;

Kandasamy, G.; Vasudevan, R.

Pharmacological Efficacy of Tamarix

aphylla: A Comprehensive Review.

Plants 2022, 11, 118. https://doi.org/

10.3390/plants11010118

Academic Editor: Noura Dosoky

Received: 17 November 2021

Accepted: 22 December 2021

Published: 31 December 2021

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plants

Review

Pharmacological Efficacy of Tamarix aphylla: AComprehensive ReviewSaad Ali Alshehri 1, Shadma Wahab 1,* , Shahabe Saquib Abullais 2, Gotam Das 3 , Umme Hani 4,Wasim Ahmad 5 , Mohd Amir 6 , Ayaz Ahmad 5, Geetha Kandasamy 7 and Rajalakshimi Vasudevan 8

1 Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;[email protected]

2 Department of Periodontics and Community Dental Sciences, College of Dentistry, King Khalid University,Abha 61421, Saudi Arabia; [email protected]

3 Department of Prosthodontics, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia;[email protected]

4 Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia;[email protected]

5 Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Safaa,Dammam 34222, Saudi Arabia; [email protected] (W.A.); [email protected] (A.A.)

6 Department of Natural Products and Alternative Medicines, College of Clinical Pharmacy, ImamAbdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; [email protected]

7 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;[email protected]

8 Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;[email protected]

* Correspondence: [email protected] or [email protected]

Abstract: Tamarix aphylla is a well-known species of the genus Tamarix. T. aphylla (Tamaricaceae) isa perennial tree in Asia, the Middle East, and Central Africa. It is used as a carminative diureticin tuberculosis, leprosy, and hepatitis. Various pharmacological properties have been shown byT. aphylla, such as antidiabetic, anti-inflammatory, antibacterial, antifungal, anticholinesterase, andwound-healing activity. However, T. aphylla has not received much attention for its secondarymetabolites and bioactive constituents. Research has shown that this plant has hidden potential thatneeds to be explored. This review aims to cover botanical classification, geographical distribution,taxonomy, ethnobotanical uses, and the phytochemical compounds found in T. aphylla. The toxicologyand pharmacological effects of T. aphylla are also discussed. We examined various scholarly resourcesto gather information on T. aphylla, including Google Scholar, Scopus, Science Direct, Springer Link,PubMed, and Web of Science. The finding of this work validates a connection between T. aphyllain conventional medicine and its antidiabetic, antibacterial, anti-inflammatory, wound-healing,antifungal, anticholinesterase, and other biological effects. T. aphylla’s entire plant (such as bark,leaves, fruits) and root extracts have been used to treat hypertension, stomach discomfort, hair loss,cough and asthma, abscesses, wounds, rheumatism, jaundice, fever, tuberculosis, and gum andtooth infection. The phytochemical screening revealed that noticeably all extracts were devoid ofalkaloids, followed by the presence of tannins. In addition, different parts have revealed the existenceof steroids, flavonoids, cardiac glycosides, and byproducts of gallic acid and ellagic acid. T. aphylla hasshown many valuable activities against different diseases and supports its traditional uses. Therefore,high-quality preclinical research and well-designated clinical trials are needed to establish the efficacyand safety of this plant in humans.

Keywords: T. aphylla; phytochemicals; biological activity; anti-inflammatory; antidiabetic; antibacterial;antifungal; anticholinesterase

Plants 2022, 11, 118. https://doi.org/10.3390/plants11010118 https://www.mdpi.com/journal/plants

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Plants 2022, 11, 118 2 of 30

1. Introduction

Natural product-based medication has been a source of treatment for various ailmentsfor thousands of years [1]. Herbal medicines have long played a vital role in developingdrugs to treat a variety of diseases. Currently, available medicines are distinctions orreproductions of constituents, combinations, and dilutions that exist in nature [2]. People’sinterest in herbal medicines is currently increasing due to fewer or no side-effects [3].Despite the minimal risk of adverse effects, the possibility of a medication interaction cannotbe rejected. Another appealing attribute for accepting a comprehensive collection of herbalmedications is cost-effectiveness. The use of herbal medicines is historical, but there is aspace in ancient traditional practices fulfilled by alternative medicine and complementarymedicines incorporating new technologies [4–6]. Therefore, we should continue to researchnew plant-based therapy from the vast reservoir of nature [7,8].

Tamaricaceae (Caryophyllales) is a family of around 80 rheophytes, halophytes, and xe-rophytes grown in semi-arid and dry regions, especially in central and southwest Asia [9,10].It is a native plant of African and Asian countries used by the locals for medicinal purposesand is commonly called tamarisk [11,12]. This plant has needle-like leaves coated in saltsecreted by the salt glands [13]. The leaf attachment on the stem and the shape of theandroecium are the most significant distinguishing features of Tamarix species: shrubs andtrees. Some morphological characteristics have intermediate states of Tamarix; therefore,it is the most taxonomically challenging genus among angiosperms [9,10]. The reportedphytochemical work on Tamarix species has shown that the main chemical constituents arepolyphenolic constituents such as flavonoids, tannins, and phenolic acids [12]. The phyto-chemical research revealed that all extracts were noticeably devoid of alkaloids, followed bythe presence of tannins. In addition, different parts of the plant have reported flavonoids,steroids, cardiac glycosides, and derivatives of ellagic acid and gallic acid [14–19]. T. aphyllahas long been used as an antipyretic, analgesic, antirheumatic, and anti-inflammatory. Gallextract has been used for throat infections and temporarily constricting the vaginal mucousmembrane before intercourse [4,14,20–22]. The bark of this plant is used to cure skin-relateddiseases, and gall on the flowers is used for its astringent effect [23]. There are various folkuses such as carminative, eczema, antimicrobial, antioxidant, aphrodisiac, anthelmintic,diuretic, anti-hemorrhoid, antidiarrheal, and skin diseases. In addition, many other studieshave exhibited activities toward inflammation, joint pain, and internal tumors [20,24]. Acomplete overview of the T. aphylla’s ethnobotanical, phytochemical, and pharmacologicalpotential is shown in Figure 1.

In this work, we reviewed the available research on T. aphylla and determined whethermodern investigation into the various properties such as antidiabetic, antibacterial, anti-inflammatory, wound-healing, antifungal, and anticholinesterase activities of this plantvalidates its use to treat these diseases. This article reviews past T. aphylla research findingsand identifies knowledge gaps that need to be addressed to fully grasp the mechanism ofaction of T. aphylla extracts in the treatment of various illnesses. In addition, the reviewcovers phytochemistry and toxicological studies, highlighting the need for more researchto back up the existing data and find new applications for this intriguing plant.

Plants 2022, 11, 118 3 of 30Plants 2022, 11, x FOR PEER REVIEW 3 of 31

Figure 1. Overview of the T. aphylla ethnobotanical, phytochemical, and pharmacological poten-tial.

2. Material Methods In the current review article, the information was collected from a literature search

using various computerized databases such as PubMed, Google Scholar, Scopus, Sci-enceDirect, and Saudi Digital Library. Keywords such as Tamarix aphylla, T. aphylla, Tam-arisk, Tamarix spp, Tamarix ethnomedicinal use, and ethnopharmacological aspects were used to search literature. In addition, keywords antimicrobial activity, biological activity, pharmacological properties, antifungal, cytotoxicity, anti-inflammatory, phytochemistry, phytochemical components, toxicology, anticholinesterase activity, and anticholinester-ase effect with respect to T. aphylla were used to search literature. Furthermore, different phrases such as “genus Tamarix in chronic diseases”, “Tamarix species in chronic disease”, “Tamarix aphylla in diabetic disease”, “Tamarix aphylla in cytotoxicity”, “analgesic activity of Tamarix aphylla”, “anticholinesterase activity of Tamarix aphylla”, “Tamarix aphylla role in inflammatory diseases”, “Tamarix aphylla role in periodontal disease”, “antifungal ac-tivity of Tamarix aphylla”, “antibacterial activity of Tamarix aphylla”, and “wound-healing activity of Tamarix aphylla” were used to search the literature related to chronic diseases. In addition, further information was retrieved from various botanical books.

3. Ethnopharmacology: Traditional Practices T. aphylla (Tamaricaceae) is the most well-known Tamarix species, reaching up to 18

m (60 feet) high. This plant is known with different names such as saltcedar, Athel tree, Athel tamarisk, and Athel pine. It is a treasure of various regions of the world including Central Africa, the Middle East, and Asia. Species of Tamarix grow in dry and hot climates, while some of its species are also found in moderate temperatures [12,13,25]. Ethnophar-macological reports on T. aphylla are presented in Table 1.

Most ethnopharmacological studies were published in Pakistan. These studies have shown that T. aphylla is used to treat various infectious diseases, including dental infec-tions, smallpox, leprosy, tuberculosis, colds, and coughs [26–28]. Many other communi-cations from other parts of the world have established that T. aphylla has antidiabetic,

Figure 1. Overview of the T. aphylla ethnobotanical, phytochemical, and pharmacological potential.

2. Material Methods

In the current review article, the information was collected from a literature searchusing various computerized databases such as PubMed, Google Scholar, Scopus, ScienceDi-rect, and Saudi Digital Library. Keywords such as Tamarix aphylla, T. aphylla, Tamarisk,Tamarix spp, Tamarix ethnomedicinal use, and ethnopharmacological aspects were usedto search literature. In addition, keywords antimicrobial activity, biological activity, phar-macological properties, antifungal, cytotoxicity, anti-inflammatory, phytochemistry, phyto-chemical components, toxicology, anticholinesterase activity, and anticholinesterase effectwith respect to T. aphylla were used to search literature. Furthermore, different phrasessuch as “genus Tamarix in chronic diseases”, “Tamarix species in chronic disease”, “Tamarixaphylla in diabetic disease”, “Tamarix aphylla in cytotoxicity”, “analgesic activity of Tamarixaphylla”, “anticholinesterase activity of Tamarix aphylla”, “Tamarix aphylla role in inflamma-tory diseases”, “Tamarix aphylla role in periodontal disease”, “antifungal activity of Tamarixaphylla”, “antibacterial activity of Tamarix aphylla”, and “wound-healing activity of Tamarixaphylla” were used to search the literature related to chronic diseases. In addition, furtherinformation was retrieved from various botanical books.

3. Ethnopharmacology: Traditional Practices

T. aphylla (Tamaricaceae) is the most well-known Tamarix species, reaching up to18 m (60 feet) high. This plant is known with different names such as saltcedar, Atheltree, Athel tamarisk, and Athel pine. It is a treasure of various regions of the worldincluding Central Africa, the Middle East, and Asia. Species of Tamarix grow in dry andhot climates, while some of its species are also found in moderate temperatures [12,13,25].Ethnopharmacological reports on T. aphylla are presented in Table 1.

Most ethnopharmacological studies were published in Pakistan. These studies haveshown that T. aphylla is used to treat various infectious diseases, including dental infections,smallpox, leprosy, tuberculosis, colds, and coughs [26–28]. Many other communications

Plants 2022, 11, 118 4 of 30

from other parts of the world have established that T. aphylla has antidiabetic, antibacterial,anti-inflammatory, and antifungal properties, in addition to being effective in periodontaldisease, along with anticholinesterase and wound-healing activities. These activities aredue to the tremendous number of phenolic compounds with astringent effects. Tamarixaphylla, together with the Aerva javanica plant, was studied ethnobotanically, chemically,and biologically in the Asir region of Saudi Arabia. The study claimed that both plantshad a high usage value (UV), indicating knowledge of the medical relevance and uses ofthese plants. In the plains and valleys (wadis) of the Asir region, T. aphylla is ubiquitous,natural, and well-grown. T. aphylla’s different parts were reported to be used in variousailments, including joint pain, skin issues, and kidney problems. Plants with a high UVreflect their extensive use by locals in the area with several therapeutic effects towardhuman health issues. As a result, the author reported that bioactive phytochemicals andother pharmacological actions should be investigated in these plants [29].

Islamic religious scripture, Holy Quran, recognizes T. aphylla with names such asAthel or Tarfaa. As a useful traditional phytotherapy for jaundice, T. aphylla leaf ash ismixed with water, which is filtered and boiled after half an hour. Salt is left behind afterwater evaporation, of which 0.5–1 g is consumed with Shurbat-e-Bazoori twice daily [23].Traditionally, the plant is known as “Mayyin Khurd” in Unani, Macheeka in Ayurveda,and Sivappattushavukku in Siddha, among other names. According to the history of folkmedicinal usage, the plant has been used for antirheumatic, analgesic, and antipyreticpurposes [4]. The folkloric assertion shows the use of T. aphylla in fever, inflammation,and pain, in addition to antimicrobial, antidiarrheal, anti-hemorrhoid, and antioxidantactivities, along with use in eczema and skin diseases, as well as an aphrodisiac, diuretic,carminative, and anthelmintic [21,23,24].To cure wounds, abscesses, and rheumatism, theleaves are boiled in water, and water is strained; then, hot leaves are tied with the affectedarea. This therapy is continued for a week. The galls are astringent, and their aqueousextract is used as a gargle to cure throat infections. An extract of the leaves is used totreat toothache [14,30]. Ethnobotanical uses include the treatment of ulcer, GIT disorders,epilepsy, hair loss, and various dermatological problems [31,32]. There is a definitivehistory of using root decoctions to cure contagious ailments, such as smallpox, tuberculosis,and leprosy. The tree’s young branch and leaf decoction are used for tetanus, spleen, andgynecological problems [33].

Table 1. T. aphylla’s ethnomedicinal usage in many places around the world.

Geographical Location Parts of the Plant Used Indication Route ofAdministration Results References

Southeastern Morocco Leaf Hypertension S/Decoction

Information was collected from therespondents of Errachidia province

regarding the plants used forhypertension, one of which

was T. aphylla.

[34]

The central region ofAbyan

governorate, YemenBark and leaf Abdominal pain, hair

loss, cough, and asthmaS, Lo/Infusion,

decoction

Ethnobotanical survey of medicinalplants showed that residents of

Yemen use T. aphylla for abdominalpain, hair loss, cough, and asthma.

[35]

Northwestern partof Pakistan Whole plant

Abscesses and wounds,rheumatism, jaundice,

bad evils

S, Lo/Decoction of ash,ash, boiled leaves

T. aphylla is one of the plantsenlisted in the Holy Quran, Islamic

literature, and Ahadith withethnobotanical relevance.

[20]

District Sargodha,Punjab, Pakistan Bark Measles, aphrodisiac S/Powdered with

oil, smokeT. aphylla is one of the most used

timber species in district Sargodha. [36]

Peshawar Valley ofPakistan Bark and leaf

Paralysis, abdominalpain, tetanus,

rheumatism, andwound healing

S, Lo/Powder extract

Ethnobotanical study on medicinalplants exhibited that residents of

Peshawar use T. aphylla invarious diseases.

[37]

District Karak, Pakistan Leaf Animal pain killer forwounds, in bird flu S/Smoke This study showed the

ethnoveterinary use of T. aphylla. [38]

Plants 2022, 11, 118 5 of 30

Table 1. Cont.

Geographical Location Parts of the Plant Used Indication Route ofAdministration Results References

Pakistan Fruit Diabetes S/Decoction T. aphylla can be used asantidiabetic medication. [39]

Karamar Valley, Swabi,Pakistan Bark

Jaundice, rheumatism,infection of gums and

teethND

T. aphylla’s extract showed activityagainst the biofilm-causing bacteria

in periodontal diseases.[27]

Chenab riverine area,Punjab province,

PakistanLeaf and bark

Cough and cold, eyeinfection,

wounds and boils,febricity

S, Lo/Poultice,

paste,decoction, ash

Local people employ T. aphylla tocure various ailments in numerous

regions of Pakistan.[26]

Rajhan Pur, Punjab,Pakistan Root, leaf

All contagious diseases,jaundice, smallpox,

leprosy, tuberculosisND A field survey showed various uses

of T. aphylla in multiple diseases. [28]

Central Sahara Shoots Aid to menstruation,postpartum care, fever S/Decoction

Results showed that peopletraditionally use T. aphylla as a

potential traditional healer.[40]

Jordan, North Badia Leaf Fever S/Decoction T. aphylla is an effective medicationin pain and inflammations. [41]

Abbreviations: T: Tamarix, L: leaf, B: bark, F: fruit, G: gall, R: root, SH: shoots, WP: whole plant, S: systemic,Lo: local, ND: not defined.

Tamarix aphylla grows widely in diverse parts of the world; therefore, its vernacularnames differ: German, Tamariske; Spanish, Taray; French, Tamaris; Arabic, Abal, Tarfaa,Ghaz, and Athel; Afrikaans, Woestyntamarisk; English, Athel pine, saltcedar, Tamarix,tamarisk, desert Tamarix, Athel tamarisk, and Athel tree [42–44].

4. Phytochemistry

This section of the review describes the structures of many secondary metabolites ofT. aphylla and the functions of these metabolites in plants and humans. These compoundscan be divided into four major biosynthetic classes: phenylpropanoids, terpenoids, al-kaloids, and polyketides. The study of phytochemicals has led to drug discovery. Theavailable literature on T. aphylla focuses on the characterization and isolation of particularparts of this plant [14,18,45,46]. A combination of phenolic chemicals characterizes thisplant material [47]. There are several uses of T. aphylla, and its preparations are used asnatural remedies to treat many diseases. Unfortunately, most of the studies have not thor-oughly investigated the phytochemicals of T. aphylla. Most research has been conducted onthe structural characterization and isolation of chemical components, including gallic acid,ellagic acid, and flavonoids [14,18,45,47–49]. Tannins and flavonoid-rich sources have beenfound in T. aphylla leaves [50].

Flavonoids and alkaloids extracted from T. aphylla have been examined for antibac-terial activity. Phytochemical screening of most extracts of T. aphylla has exhibited thepresence of tannins and a lack of alkaloids. Bioactive mixtures and metabolites have beenfound, such as cardiac glycosides, flavonoids, terpenoids, and steroids. Gallic and ellagicacid are derivatives of this plant species [15–17,19]. The leaves and stems of T. aphyllahave a comparable phytochemical composition. Nevertheless, quantitative analyses haveindicated that the leaves have a considerably greater quantity of polyphenols than thestems [17]. A floral extract of T. aphylla yielded isoferulic acid, 3-O-beta-glucopyranoside,glycosylated isoferulic acid, and novel phenolics such as dehydrodigallic acid dimethylester and tamarixetin 3,3’-disodium sulfate. According to the spectral data, their structureswere developed [18]. Various studies have shown structural derivatives among hydrolyz-able tannins [51]. T. aphylla galls, on the other hand, generate the ellagitannin tamarixellagicacid [49]. According to a study, under an abiotic stress environment, a halophytic plantstimulates oxidative stress reactive oxygen species in hostile conditions. Therefore, timeand collection area are factors that may significantly change the amounts of secondarymetabolites [17,49,52]. Table 2 lists a few important secondary metabolites of T. aphylla.

Plants 2022, 11, 118 6 of 30

Table 2. Some of the primary and secondary metabolites of T. aphylla.

Phytochemical Category Phytochemical Name Structure Part/Extract References

Aromatic hydrocarbonCarbohydrate Fructose

Plants 2022, 11, x FOR PEER REVIEW 6 of 31

indicated that the leaves have a considerably greater quantity of polyphenols than the stems [17]. A floral extract of T. aphylla yielded isoferulic acid, 3-O-beta-glucopyranoside, glycosylated isoferulic acid, and novel phenolics such as dehydrodigallic acid dimethyl ester and tamarixetin 3,3’-disodium sulfate. According to the spectral data, their struc-tures were developed [18]. Various studies have shown structural derivatives among hy-drolyzable tannins [51]. T. aphylla galls, on the other hand, generate the ellagitannin tamarixellagic acid [49]. According to a study, under an abiotic stress environment, a hal-ophytic plant stimulates oxidative stress reactive oxygen species in hostile conditions. Therefore, time and collection area are factors that may significantly change the amounts of secondary metabolites [17,49,52]. Table 2 lists a few important secondary metabolites of T. aphylla.


Phytochemical Category

Phytochemical Name

Structure Part/Extract Reference

Aromatic hydrocar-bon

Carbohydrate Fructose OH

OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53]

G, Gu/EtAc [53]

Glucose





Phytochemical Name




OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53]

G, Gu/EtAc [53]

Raffinose





Phytochemical Name




OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53]

G/EtAc [53]

Ribose





Phytochemical Name




OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53]

G/EtAc [53]

Sucrose





Phytochemical Name




OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53]

G/EtAc [53]

Xylose





Phytochemical Name




OH

OOH

OHOH

G, Gu/EtAc [53]

Glucose OH

OH

OH

H

OH H

OH

H

H

OH

G, Gu/EtAc [53]

Raffinose

O

O

O

OH OHOO

OH

OH

OH

OH

OH

OH

OH

OH

OH

G/EtAc [53]

Ribose

OH

OH

OH

OH O

G/EtAc [53]

Sucrose O

O

OH OHO

OH

OH

OHOH

OH

OH

G/EtAc [53]

Xylose

OH

OH

OH

OH O

G, Gu/EtAc [53] G, Gu/EtAc [53]

Plants 2022, 11, 118 7 of 30

Table 2. Cont.


Flavonoids Apigenin


Flavonoids Apigenin OOH

OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH

L, S, B/EtOH, aqueous [17,55]

Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH

L and S/MeOH, EtOH [17,55]

Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]

SS, L, B, EtOH [54]

Isoquercetin



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]

G/EtAc [53]

Isorhamnetin



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]


Juglanin



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]

G/EtAc [53]

Kaempferide



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]

Ap/EtOH [17,55,56]

Kaempferol



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]


Plants 2022, 11, 118 8 of 30

Table 2. Cont.


Luteolin



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56]

L and S, EtOH [17]

Quercetin



OH O

OH

SS, L, B, EtOH [54]

Isoquercetin

O

O

OH

OH

OH

OH

O

O OH

OH

OHOH

G/EtAc [53]

Isorhamnetin

CH3O

OH

OOH

OH O

OH


Juglanin O

O

O

OH

OHOH

OOH

OH

OH

G/EtAc [53]

Kaempferide O

O

OH

OH

OH

OCH3

Ap/EtOH [17,55,56]

Kaempferol OOH

OH O

OH

OH


Luteolin OOH

OH O

OH

OH

L and S, EtOH [17]

Quercetin O

O

OH

OH

OH

OH

OH

SS, L/EtOH [17,56] SS, L/EtOH [17,56]

Quercetin dimethyl ether


Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]

Quercetin-3-rhamnoside

CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH

L and S/MeOH, EtOH [54]

Phenolic acid Caffeic acid

OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH

G/aqueous etha-nolic acid [49]

Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]

L/Aqueous [55]



Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]

F/EtOH [57]

Quercetin3-O-galactoside


Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]




Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]

L and S, EtOH [17]

Plants 2022, 11, 118 9 of 30

Table 2. Cont.


Dehydrodigallic acid


Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]

G, EtAc [53]

Dehydrotrigallic acid


Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53]

G/aqueous ethanolic acid [49]

Ellagic acid


Quercetin dime-

thyl ether O

O

o

OH

O

OH

OH

L/Aqueous [55]


CH3

O

O

O

OH

OH

OH

OH O HOH

H

OH

H

OHH

H

F/EtOH [57]

Quercetin 3-O-ga-

lactoside

OOH

OH

O

O

OH

OH

OH

OHOOH

OH



OH

O

OH

OH

L and S, EtOH [17]

Dehydrodigallic

acid O

OH

OH

OH

COOH

COOH

OHOH

G, EtAc [53]

Dehydrotrigallic

acid

O

OH

O

OH

COOH

COOH

OHOH

OH

OHOH

COOH


Ellagic acid

O

O

OH

OH

O

O

OH

OH

G, debarked heart-

wood [53] G, debarked heartwood [53]

Gallic acid


Gallic acid

OH

OH

OH

O

OH

L, debarked heart-wood [55]

Isoferulic acid

CH3O

OH

O

OH

Debarked heart-wood, G, EtAc [53]

p-Coumaric acid OH

O

OHH

L and S/EtOH, aqueous

[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH

L, debarked heart-wood/aqueous [55]

Phenolic glycoside Dehydrodigallic-xanthone

O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]

Dehydrotrigallic-xanthone

O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]

Abbreviations: G: gall, L: leaf, S: stem, F: flower, B: bark, Sh: shoot, Ap: aerial parts, Pet: petro-leum, EO: essential oil, Gu: gum, R: root, Aq: aqueous, EtOH: ethanol, MeOH: methanol, EtAc: ethyl acetate.

L, debarked heartwood [55]

Isoferulic acid


Gallic acid

OH

OH

OH

O

OH


Isoferulic acid

CH3O

OH

O

OH


p-Coumaric acid OH

O

OHH


[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH



O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]


O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]


Debarked heartwood, G,EtAc [53]

p-Coumaric acid


Gallic acid

OH

OH

OH

O

OH


Isoferulic acid

CH3O

OH

O

OH


p-Coumaric acid OH

O

OHH


[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH



O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]


O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]


L and S/EtOH,aqueous [17,55]

Plants 2022, 11, 118 10 of 30

Table 2. Cont.


Syringic acid


Gallic acid

OH

OH

OH

O

OH


Isoferulic acid

CH3O

OH

O

OH


p-Coumaric acid OH

O

OHH


[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH



O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]


O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]


L, debarkedheartwood/aqueous [55]



Gallic acid

OH

OH

OH

O

OH


Isoferulic acid

CH3O

OH

O

OH


p-Coumaric acid OH

O

OHH


[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH



O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]


O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]


G/Aq-EtOH [49]



Gallic acid

OH

OH

OH

O

OH


Isoferulic acid

CH3O

OH

O

OH


p-Coumaric acid OH

O

OHH


[17,55]

Syringic acid

C H 3

O

O H

OC H 3

OOH



O

OH

OH

COOH

OHOH

O

OH

G/Aq-EtOH [49]


O

OH

O

OH

COOH

OHOH

OH

OHOH

O O

G/Aq-EtOH [49]


G/Aq-EtOH [49]

Abbreviations: G: gall, L: leaf, S: stem, F: flower, B: bark, Sh: shoot, Ap: aerial parts, Pet: petroleum, EO: essentialoil, Gu: gum, R: root, Aq: aqueous, EtOH: ethanol, MeOH: methanol, EtAc: ethyl acetate.

5. Pharmacological Efficacy of Tamarix aphylla5.1. Anti-Inflammatory Activity

Inflammation is the body’s reaction to fight burns, injuries, toxic stimuli, and infectionsthat emerge as anorexia, fever, and edema. Inflammation is the body’s first defense reactionthat removes undesirable effects and commences the healing operations. This protectivesystem is crucial for a healthy and normal physiological state. Inflammation can be acuteor chronic [58,59]. Removing the damaged stimuli is the treatment of acute inflammatoryconditions; however, unchecked acute inflammation can lead to chronic inflammation. Achronic inflammatory response can cause serious health problems, such as neurologicaland cardiovascular diseases and cancer [60]. Alzheimer’s disease, cardiovascular disease,metabolic disorders, allergies, malignancies, and autoimmune illnesses all have chronic in-flammation as a contributing factor [61]. Anti-inflammatory medications, both nonsteroidaland steroidal, are the most prescribed treatments. In most documented cases, the long-termuse of these medicines is hampered by their side-effects, necessitating the therapeutic useof less toxic solutions with fewer unpleasant responses [62,63]. Consequently, there is arequirement for effective, safe, and cost-effective alternative therapies.

Herbal therapy has been used to treat various ailments since ancient times, includingchronic inflammatory diseases. Medicinal plants contain anti-inflammatory properties andhave limited or no adverse effects [3]. T. aphylla is generally safe and harmless to humans.However, inflammation is a significant development in many illnesses [64]. Consequently,there is a persistent need to learn more about the benefits of natural medications in treatinginflammatory diseases to expand our scientific awareness. Tamarix species possess variouscompounds such as phenolic acids, tannins, sulfur-containing compounds, and flavonoids,which have been used since ancient times to cure chronic inflammatory disorders [11,12].T. aphylla is an encouraging herbal medication with a wide range of metabolites, manymedical uses, and pharmacological assurance. The aqueous ethanolic extract of T. aphylla

Plants 2022, 11, 118 11 of 30

galls has been shown to have anti-inflammatory and antipyretic properties [4]. The inflam-matory pathway and probable role of T. aphylla as an anti-inflammatory drug are illustratedin Figure 2.


5. Pharmacological Efficacy of Tamarix aphylla 5.1. Anti-Inflammatory Activity

Inflammation is the body’s reaction to fight burns, injuries, toxic stimuli, and infec-tions that emerge as anorexia, fever, and edema. Inflammation is the body’s first defense reaction that removes undesirable effects and commences the healing operations. This protective system is crucial for a healthy and normal physiological state. Inflammation can be acute or chronic [58,59]. Removing the damaged stimuli is the treatment of acute inflammatory conditions; however, unchecked acute inflammation can lead to chronic in-flammation. A chronic inflammatory response can cause serious health problems, such as neurological and cardiovascular diseases and cancer [60]. Alzheimer’s disease, cardiovas-cular disease, metabolic disorders, allergies, malignancies, and autoimmune illnesses all have chronic inflammation as a contributing factor [61]. Anti-inflammatory medications, both nonsteroidal and steroidal, are the most prescribed treatments. In most documented cases, the long-term use of these medicines is hampered by their side-effects, necessitating the therapeutic use of less toxic solutions with fewer unpleasant responses [62,63]. Con-sequently, there is a requirement for effective, safe, and cost-effective alternative thera-pies.

Herbal therapy has been used to treat various ailments since ancient times, including chronic inflammatory diseases. Medicinal plants contain anti-inflammatory properties and have limited or no adverse effects [3]. T. aphylla is generally safe and harmless to hu-mans. However, inflammation is a significant development in many illnesses [64]. Conse-quently, there is a persistent need to learn more about the benefits of natural medications in treating inflammatory diseases to expand our scientific awareness. Tamarix species pos-sess various compounds such as phenolic acids, tannins, sulfur-containing compounds, and flavonoids, which have been used since ancient times to cure chronic inflammatory disorders [11,12]. T. aphylla is an encouraging herbal medication with a wide range of me-tabolites, many medical uses, and pharmacological assurance. The aqueous ethanolic ex-tract of T. aphylla galls has been shown to have anti-inflammatory and antipyretic proper-ties [4]. The inflammatory pathway and probable role of T. aphylla as an anti-inflammatory drug are illustrated in Figure 2.

Figure 2. Inflammatory pathway and the probable role of T. aphylla as an anti-inflammatory agent. Figure 2. Inflammatory pathway and the probable role of T. aphylla as an anti-inflammatory agent.

ROS: Reactive oxygen species, TNF-α: Tumor necrosis factor alpha, NO: Nitric oxide, IL-1: Interleukin-1, IL-6: Interleukin-6.

An investigation was carried out to examine the modulatory effect of T. aphylla, inwhich bioassay-guided isolation was carried out on several inflammatory indicators suchas TNF-α and ROS, proliferation of lymphocyte T cells, and proinflammatory cytokines.The aqueous extract of T. aphylla suppressed intracellular ROS production, NO generation,and T-cell proliferation. The most effective inflammatory markers were the liquid–liquidfractional method partitioned aqueous ethanolic crude extract and n-BuOH and DCMextracts. In addition, 3,5-dihydroxy-4-methoxy benzoic acid methyl ester from the DCMextracts suppressed the generation of ROS and TNF-α. Furthermore, all mediators exam-ined demonstrated inhibitory action in the presence of kaempferol. Therefore, T. aphyllaconstituents might be used as anti-inflammatory medications [63].

5.2. Wound-Healing Activity

The sequence of interconnected processes that replace damaged tissue at the injury sitewith newly produced tissue is called wound healing. Regular biological action is attainedthrough four remarkably programmed stages: hemostasis, inflammation, proliferation,and remodeling. All four stages must happen in a certain time frame with a propersequence to heal the wound. Many factors affect the process of wound healing, such asinfection, oxygenation, sex hormones, age, stress, obesity, alcoholism, nutrition, smoking,and diabetes [65]. Various studies have proven that natural products affect all these factors.Natural therapeutics promote wound healing and fix impaired wounds with lessened sideeffects. Natural products have been used since ancient times to heal wounds due to their

Plants 2022, 11, 118 12 of 30

pharmacological importance, such as antibacterial, anti-inflammatory, and cell-stimulatingpotential [66]. The effectiveness of these natural products has been examined throughin vitro, in vivo, and human studies. Skin wound healing is a perplexing biological activityand a coordinated cellular and biochemical sequence. Combining herbal materials withadvanced drugs has improved regeneration [67].

T. aphylla’s anti-inflammatory and wound-healing properties are reported in Islamicliterature and other resources from far-flung regions of Saudi Arabia. In the Al-Qassimregion of Saudi Arabia, dried powders of all plant parts are used for 1 week to treat camelskin disorder (allergic or mycotic dermatitis) [68]. Burnt smoke from the dried pulverizedplant leaves has history as an injury-healing agent and a dental painkiller [30]. It wasfound that boiling plant leaves and tying them to afflicted skin manages abscesses andrheumatism, in addition to wound healing [23]. An animal study examined an ethanolicextract of T. aphylla for wound-healing activity. A linear incision and a circular excisionwere employed to assess wound healing. Total protein estimation, antioxidant activity, lipidperoxides, uronic acid, hexosamine, and the tensile strength of tissue from incision woundswere examined. The period of epithelialization and TNF-α concentration of the woundtissues were also assessed in this study. Compared to conventional medication, the extracttreatment groups exhibited considerable antibacterial activity. Results of the study showedthat T. aphylla extract substantially enhanced the collagen content and remarkably increasedtensile strength. T. aphylla extract has been shown to prevent oxidative damage, speed uphealing activity, and have potent antioxidant properties. The epithelialization duration ofthe treated wounds was reduced by 40%. The study’s findings showed that the ethanolicextract of T. aphylla has strong wound-healing ability [69]. Another study investigatedthe wound-healing potential of T. aphylla extract by adopting the induced paw edemamodel in Wistar rats. In addition, the gel base of a T. aphylla extract, namely, Carbapol-934, was employed to investigate carrageen-induced anti-inflammatory properties. Thisexamination showed that T. aphylla has wound-healing, anti-inflammatory, and antioxidantproperties [70]. There is an urgent need to determine the actual mechanism of action, thesafety, and the adverse effects of T. aphylla and its secondary metabolites; furthermore, thereis a demand for revamped purification techniques, innovative extraction methods, andquality control evaluation with treatment regimes. Although T. aphylla is less expensivethan current therapies, it is susceptible to geographic location, season, and batch-to-batchfluctuation, resulting in unanticipated allergic responses and adverse effects. The possiblemechanism of T. aphylla wound-healing activity is shown in Figure 3.

5.3. Antibacterial Activity

In tropical and subtropical areas, human diseases, particularly those involving mi-croorganisms such as bacteria, fungus, viruses, and nematodes, inflict significant harm.Over the last two decades, there has been a surge in interest in natural products as potentialsources of novel antimicrobial agents. Consequently, various extracts from conventionalherbal drugs have been examined to discover numerous pharmacological benefits [71–73].Moreover, there is a need for novel herbal extracts and natural medicines that might ef-fectively resist bacteria [71,74]. The antibacterial properties of plant phytochemicals havedemonstrated their therapeutic usefulness in treating bacterial infections [75,76]. There-fore, documentation of the constituents and antibacterial activity of medicinal plants isprecious since it may be utilized to conduct additional research to develop innovativeantibacterial treatments.

Therefore, it is necessary to explore the phytochemical constituents of T. aphylla totreat infections [77]. This section aims to explore the antibacterial activities of extracts andsecondary metabolites of T. aphylla to bridge existing research gaps, to provide suggestionsbased on the current understanding of T. aphylla’s advantages, and to advise more scientificresearch for innovative antibacterial treatments. All the secondary metabolites of T. aphyllalisted in this review have medicinal properties, thus authenticating their usage [78]. For

Plants 2022, 11, 118 13 of 30

future study and the formation of new antibiotics to fight resistant pathogenic bacteria, allrelated studies of T. aphylla are discussed.


innovative extraction methods, and quality control evaluation with treatment regimes. Although T. aphylla is less expensive than current therapies, it is susceptible to geographic location, season, and batch-to-batch fluctuation, resulting in unanticipated allergic re-sponses and adverse effects. The possible mechanism of T. aphylla wound-healing activity is shown in Figure 3.

Figure 3. Probable mechanism of T. aphylla wound-healing activity.

5.3. Antibacterial Activity In tropical and subtropical areas, human diseases, particularly those involving mi-

croorganisms such as bacteria, fungus, viruses, and nematodes, inflict significant harm. Over the last two decades, there has been a surge in interest in natural products as poten-tial sources of novel antimicrobial agents. Consequently, various extracts from conven-tional herbal drugs have been examined to discover numerous pharmacological benefits [71–73]. Moreover, there is a need for novel herbal extracts and natural medicines that might effectively resist bacteria [71,74]. The antibacterial properties of plant phytochemi-cals have demonstrated their therapeutic usefulness in treating bacterial infections [75,76]. Therefore, documentation of the constituents and antibacterial activity of medicinal plants is precious since it may be utilized to conduct additional research to develop innovative antibacterial treatments.

Therefore, it is necessary to explore the phytochemical constituents of T. aphylla to treat infections [77]. This section aims to explore the antibacterial activities of extracts and secondary metabolites of T. aphylla to bridge existing research gaps, to provide sugges-tions based on the current understanding of T. aphylla’s advantages, and to advise more scientific research for innovative antibacterial treatments. All the secondary metabolites of T. aphylla listed in this review have medicinal properties, thus authenticating their us-age [78]. For future study and the formation of new antibiotics to fight resistant pathogenic bacteria, all related studies of T. aphylla are discussed.

The antibacterial activity of a methanolic extract of T. aphylla bark against microbial strains in a study provided scientific evidence for the use of its phytoconstituents as an antimicrobial treatment. Halophytic species with stimulant and hepatotoxic properties are

Figure 3. Probable mechanism of T. aphylla wound-healing activity.

The antibacterial activity of a methanolic extract of T. aphylla bark against microbialstrains in a study provided scientific evidence for the use of its phytoconstituents as anantimicrobial treatment. Halophytic species with stimulant and hepatotoxic propertiesare used to treat liver-related ailments. Halophytic species suppressed all bacterial strains,leaving Listeria monocytogenes, and studies have shown that polar methanolic fractions aremore effective than polar chloroform fractions [79]. A study was conducted to test theantibacterial activity against 10 pathogenic bacteria implicated in severe ailments affectinghumans and animals. Fresh and disease-free T. aphylla leaves were accumulated fromSaudi Arabia’s various geographical locations. The antibacterial screening effectivenessof T. aphylla leaves against multidrug-resistant human infections was studied in vitro. Theantibacterial effects of the methanol and ethanol leaf extracts were different and showedvarying inhibitory effects against the examined pathogenic strains, ranging from modestinhibition (4 ± 0.6 mm) to high inhibition (20.7 ± 1.3 mm). There were no significant varia-tions in the lowest inhibitory concentrations of ethanol and methanol extracts. T. aphyllacontains antibacterial biomolecules that might be used to combat multidrug-resistant hu-man infections [80]. The methanolic extract of T. aphylla and its phytochemical constituentswere explored in vitro for antibacterial activity against various microbial strains. The discdiffusion assay with 25, 50, 75, and 100 mg/mL stock solutions was employed to exam-ine the antibacterial activity toward Escherichia coli, Bacillus subtilis, Salmonella typhi, andStaphylococcus aureus, in addition to antifungal activity toward strains such as Aspergillusflavus and Candida albicans. The extract’s inhibitory efficacy in millimeters was calculatedby measuring the zone of growth inhibition surrounding the discs and comparing it to thereference medication. The study showed that T. aphylla bark extract has a more significantinhibition zone at higher concentrations [81]. These compelling results can motivate healthworkers to use bioactive materials and phytoconstituents.

Biofilms are multispecies bacterial colonies that invade the oral cavity as plaque,causing dental cavities and periodontal disease [82]. In one study, three herbs were exam-ined to determine their effectiveness against pinpointed dental biofilm-forming bacteria.Pathogenic strains that form dental biofilms were isolated, grown, and evaluated using

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PCR-based 16S ribosomal RNA (or 16S rRNA) nucleotide sequences. T. aphylla L., Meliaazadirachta L., and Acacia arabica were the three crucial medicinal plants investigated todetermine their antibacterial activity toward biofilm-forming strains. The findings showedthat extracts of these three medicinal plants can be utilized against pathogenic bacteria thatcause dental biofilms, and pharmaceutical companies should include them in dental careproducts [27]. The leaves of T. aphylla have been characterized as a rich source of tanninsand flavonoids [50]. Kaempferol is a phytochemical found in T. aphylla. It has several thera-peutic properties such as anticancer and antioxidant activities, while its usage is limitedbecause of low permeability and poor solubility [83]. Kaempferol and resveratrol are twophenolic compounds that have shown antimicrobial activity. Therefore, researchers haveemployed two methods, time to kill and checkerboard, to evaluate this property. Studiesshowed that both compounds inhibited growth in MHB (Muller–Hilton broth) and milkaccording to the time-to-kill method [84]. In another study, T. aphylla suppressed the in-crease in microorganisms such as S. aureus and P. aeruginosa [69]. The possible antibacterialmechanism of T. aphylla is shown in Figure 4.

5.4. Antifungal Activity

Fungal infections are among the most dangerous diseases, killing around 1.5 millionhumans each year worldwide [85]. Infection of the skin ranks fourth among all fungalillnesses, and it also accounts for the bulk of deaths [86,87]. In the last several years, therehas been an increase in the frequency of fungal illnesses and the resistance of specificfungus species to various fungicides used in medicine. Furthermore, fungi are among themost underappreciated diseases, while the reality is that amphotericin B and alternativecommercially available antifungal therapies are still considered the gold standard. However,antifungal medicines have various side-effects such as toxicity, effectiveness, price, andextensive usage, resulting in resistant strains [88]. Resistance to antifungal medicationshas become a common issue because of their overuse. Therefore, plant-based therapieshave piqued the interest of experts as a potential therapy for fungal infections [5]. Theplant world has long been a hotbed for numerous natural chemicals with unique structures,which has piqued researchers’ curiosity in studying various plant species to this day.Numerous studies have shown that plants are a source of bioactive secondary metabolites,such as alkaloids, terpenoids, and saponins, all of which have demonstrated antifungalactivities [89]. Traditional systems of medicine have also reported that medicinal herbsare fruitful candidates for treating animal and human mycoses. Furthermore, they can beused to develop novel antifungal drugs [88]. Accordingly, this section aims to explain thecurrent situation regarding T. aphylla and its antifungal compounds, which may help todevelop more effective antifungal medicines in the future.

A study was conducted to determine the effectiveness of ethanolic extracts of T. aphylla(2000 ppm, 1000 ppm, and 500 ppm) against six pathogenic fungi: Fusarium oxysporum,Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Saccharomyces cerevisiae, and Penicil-lium notatum. Five different solvents (methanol, ethanol, acetone, chloroform, and distilledwater) were used. The percentage suppression of fungus growth was shown to be dose-dependent. Terbinafine (synthetic drug) was administered in typical dosages with distilledwater to test its effect against the various fungi. Terbinafine constrained the increase in A.flavus, A. fumigatus, A. niger, F. oxysporum, P. notatum, and S. cerevisiae at concentrations of65 ± 0.58, 72± 1.00, 70± 1.15, 59± 1.00, 60± 0.58, and 80± 0.58 (µg/mL of PDA medium),respectively. The most effective solvent was chloroform, which prevented 97.68% ± 0.58%growth of F. oxysporum, 9.37% ± 0.33% growth of A. niger, 92.68% ± 3.33% growth ofS. cerevisiae, 91.46% ± 2.08% growth of A. fumigatus, 88.48% ± 0.88% growth of A. flavus,and 87.95% ± 1.15% growth of P. notatum. Outcomes were statistically correlated to anegative control group, and most effects were highly significant (p ≤ 0.000). The stem–barkextract of T. aphylla showed the highest percentage of suppression with chloroform, fol-lowed by ethanol, acetone, methanol, and distilled water [90]. The methanolic extract ofthe bark of T. aphylla was examined in a study to counter bacterial pathogens in vitro to

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validate as Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella typhi, andfungal strains Candida albicans and Aspergillus flavus were tested using the disc diffusionassay with 25, 50, 75, and 100 mg/mL stock solutions prepared in dimethyl sulfoxide.The extract’s inhibitory impact in millimeters was calculated by measuring the zone ofgrowth inhibition surrounding the discs and comparing it to the reference medication.T. aphylla bark established a marked zone of inhibition at higher concentration for mostfungal and bacterial strains. According to the findings, T. aphylla produces bioactive andphytochemical substances used in healthcare [81]. However, there is a scarcity of researchand comprehensive reviews on T. aphylla as an alternative to antifungal medications. Thereis a need to study the structure–activity relationship, molecular mechanism, and potentialsynergistic effects of components of T. aphylla. These findings suggest the need for furtherresearch on T. aphylla to manage antifungal diseases.


Figure 4. Possible antibacterial mechanism of T. aphylla against clinically important pathogens.

5.4. Antifungal Activity Fungal infections are among the most dangerous diseases, killing around 1.5 million

humans each year worldwide [85]. Infection of the skin ranks fourth among all fungal illnesses, and it also accounts for the bulk of deaths [86,87]. In the last several years, there has been an increase in the frequency of fungal illnesses and the resistance of specific fun-gus species to various fungicides used in medicine. Furthermore, fungi are among the most underappreciated diseases, while the reality is that amphotericin B and alternative commercially available antifungal therapies are still considered the gold standard. How-ever, antifungal medicines have various side-effects such as toxicity, effectiveness, price, and extensive usage, resulting in resistant strains [88]. Resistance to antifungal medica-tions has become a common issue because of their overuse. Therefore, plant-based thera-pies have piqued the interest of experts as a potential therapy for fungal infections [5]. The plant world has long been a hotbed for numerous natural chemicals with unique structures, which has piqued researchers’ curiosity in studying various plant species to this day. Numerous studies have shown that plants are a source of bioactive secondary metabolites, such as alkaloids, terpenoids, and saponins, all of which have demonstrated antifungal activities [89]. Traditional systems of medicine have also reported that

Figure 4. Possible antibacterial mechanism of T. aphylla against clinically important pathogens.

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5.5. Periodontal Disease

After dental caries, periodontitis is the second most prevalent dental disease world-wide [91,92]. It is caused by forming an organized biofilm of bacterial strain, so-calleddental plaque, in the subgingival area, affixed to host tissues and cells. This ultimatelyresults in loss of supporting tooth structure [93,94]. The most common cause of periodontaldiseases is infection and inflammation of the alveolar bone and gingiva, which supportsthe tooth in the socket [95]. Gingivitis is a disease of the gums in which they become redand swollen with a high bleed tendency without loss of supporting tooth structure [96–98].Adults are more likely to get periodontal disease, mainly slow and moderately progressiveperiodontitis. Biofilms are multispecies bacterial colonies that invade the oral cavity asplaque, causing dental cavities and periodontal disease [99]. In a study, three herbs wereexamined to determine the effectiveness against pinpointed dental biofilm-forming bacteria.Pathogenic strains that form dental biofilm were isolated, grown, and evaluated usingPCR-based 16S ribosomal RNA (or 16S rRNA) nucleotide sequences [27].

T. aphylla, Melia azadirachta, and Acacia arabica were the three crucial medicinal plants in-vestigated to determine their antibacterial activity against biofilm-forming strains. The find-ings showed that extracts of these three medicinal plants can be utilized against pathogenicbacteria that cause dental biofilms. Phylogenetic examinations explored 19 strains linkedto Firmicutes, Actinobacteria, and Proteobacteria. Eleven of the 19 isolates were discoveredto have a strong biofilm-forming potential, and an antibiotic activity assay revealed thatthe chosen herbs suppressed their development. Therefore, the findings showed thatextracts of these medicinal plants can be utilized to guard against pathogenic bacteria thatcause dental biofilms. Therefore, pharmaceutical companies should include them in dentalcare products [27]. Periodontal disease and the probable role of T. aphylla are illustratedin Figure 5.


revealed that the chosen herbs suppressed their development. Therefore, the findings showed that extracts of these medicinal plants can be utilized to guard against pathogenic bacteria that cause dental biofilms. Therefore, pharmaceutical companies should include them in dental care products [27]. Periodontal disease and the probable role of T. aphylla are illustrated in Figure 5.

Figure 5. Periodontal disease and the probable role of T. aphylla.

5.6. Anticholinesterase Activity Anticholinesterases are a class of medicines that inhibit acetylcholinesterase from de-

stroying the neurotransmitter acetylcholine in the nervous system. Acetylcholine is a neu-rotransmitter that operates in the parasympathetic nervous system. It is part of the auto-nomic nervous system due to which smooth muscle contraction, secretion, and blood ves-sel dilation occur. Anticholinesterase prevents acetylcholine from being destroyed, allow-ing elevated levels of the neurotransmitter to accumulate at the spots of the mechanism. As a result, it provokes the parasympathetic nervous system, drops the heart rate, de-creases blood pressure, stimulates secretion, and activates smooth muscle compression. The most beneficial application of anticholinesterase as a family of medications is in the treatment of Alzheimer’s disease, where decreased acetylcholine transmission contributes to the illness’s neuropathology [100].

Major constituents of T. aphylla include polyphenols, triterpenes, tamarixellagic acid, and dehydrotrigallic and dehydrodiagllic acids [12,101]; they have a potential role in pre-venting chronic and degenerative diseases. Traditional medicine uses Tamarix species as a stimulant of perspiration, an astringent, and a diuretic. The biological activities of sev-eral T. aphylla extracts were investigated in comparative research. At the measured con-centration of 1110.00 g/mL and under the assay conditions, inhibitory percentages of 21.00%, 11.20%, and 9.16% were established for AcOEt, EtOH, and MeOH leaf extracts, respectively, with modest activity against AChE. Stem extracts were prepared using the same solvents and revealed inhibitory percentages of 16.19% (AcOEt), 17.45% (EtOH), and 10.20% (MeOH). In the case of butyrylcholinesterase (BuChE), T. aphylla extracts were in-effective in terms of inhibition. When it came to inhibiting AChE and BuChE, the exam-ined extracts were less effective than the positive control galantamine, which was evalu-ated under identical circumstances (IC50 = 1.95 and 4.71 µg/mL, respectively). The absence of action against BuChE and the modest activity of the studied extracts against AChE can be explained by the potential antagonism of physiologically active p-coumaric acid (only detected in the AcOEt extract), with high anti-ChE activity against both BuChE and AChE

Figure 5. Periodontal disease and the probable role of T. aphylla.

5.6. Anticholinesterase Activity

Anticholinesterases are a class of medicines that inhibit acetylcholinesterase fromdestroying the neurotransmitter acetylcholine in the nervous system. Acetylcholine is aneurotransmitter that operates in the parasympathetic nervous system. It is part of theautonomic nervous system due to which smooth muscle contraction, secretion, and bloodvessel dilation occur. Anticholinesterase prevents acetylcholine from being destroyed, al-

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lowing elevated levels of the neurotransmitter to accumulate at the spots of the mechanism.As a result, it provokes the parasympathetic nervous system, drops the heart rate, decreasesblood pressure, stimulates secretion, and activates smooth muscle compression. The mostbeneficial application of anticholinesterase as a family of medications is in the treatment ofAlzheimer’s disease, where decreased acetylcholine transmission contributes to the illness’sneuropathology [100].

Major constituents of T. aphylla include polyphenols, triterpenes, tamarixellagic acid,and dehydrotrigallic and dehydrodiagllic acids [12,101]; they have a potential role inpreventing chronic and degenerative diseases. Traditional medicine uses Tamarix species asa stimulant of perspiration, an astringent, and a diuretic. The biological activities of severalT. aphylla extracts were investigated in comparative research. At the measured concentrationof 1110.00 g/mL and under the assay conditions, inhibitory percentages of 21.00%, 11.20%,and 9.16% were established for AcOEt, EtOH, and MeOH leaf extracts, respectively, withmodest activity against AChE. Stem extracts were prepared using the same solvents andrevealed inhibitory percentages of 16.19% (AcOEt), 17.45% (EtOH), and 10.20% (MeOH).In the case of butyrylcholinesterase (BuChE), T. aphylla extracts were ineffective in termsof inhibition. When it came to inhibiting AChE and BuChE, the examined extracts wereless effective than the positive control galantamine, which was evaluated under identicalcircumstances (IC50 = 1.95 and 4.71 µg/mL, respectively). The absence of action againstBuChE and the modest activity of the studied extracts against AChE can be explained by thepotential antagonism of physiologically active p-coumaric acid (only detected in the AcOEtextract), with high anti-ChE activity against both BuChE and AChE [102]. There are manyother unidentified compounds, but polar MeOH and EtOH extracts are rich in ellagic andgallic acids, which have been proclaimed as effective blockers of AChE [46]. Mahfoudhiet al. exhibited that activity toward superoxide anion radicals (O2−), DPPH radicals, andnitric oxide radicals (•NO) was accomplished in a concentration-dependent mode. T. aphyllaalso had modest anti-acetylcholinesterase activity but no anti-butyrylcholinesterase effects.MeOH extracts had IC50 values ranging from 8.41 to 24.81 g/mL against α-glucosidase [54].

5.7. Analgesic Activity

Pain is an unpleasant sensation because of actual or prospective tissue injury. Theexperience of pain is produced in the early stages via direct activation of sensory nervefibers. Contrastingly, inflammatory mediators are the main cause of trouble in the laterstages. Contemporary anti-inflammatory and antipain medications are helpful, but theyhave serious side-effects including anemia, ulcers, endocrine disruption, and osteoporosis.On the other hand, numerous prospective phytoconstituents from herbs have shownanalgesic activities; therefore, people are more interested in medicinal plants than syntheticmedicines. In addition, these plants generally have adequate biological activity with feweradverse effects [103].

In this section, we review the analgesis activity of T. aphylla. The findings of thissection allow identifying T. aphylla and its secondary metabolites, which can be helpful inclinically advanced herbal drugs as analgesics with fewer adverse effects and improvedbioavailability. One study examined the analgesic effect of an aqueous ethanol (70:30)extract of T. aphylla aerial parts prepared using cold maceration. The study investigatedanalgesic efficacy in mice using eddy’s hot plate method, formalin-induced paw licking,and the acetic acid-induced writhing. When compared to the normal control, the aqueousethanol extract of T. aphylla inhibited 42% (p < 0.005) of acetic acid-induced writhing,63% (p < 0.005) of formalin-induced paw licking, and 42% (p < 0.005) of response time.Outcomes of the examination showed that the aqueous ethanolic extract of T. aphylla haspromising analgesic properties [21]. The results of this study encourage the applicationof T. aphylla to alleviate fever and pain. Moreover, more examinations are required toestablish the cellular mechanisms and classify the constituents of structurally effectivesubstances for standardization. Another study was conducted in Khartoum, Sudan, for6 months. The Phyto-342 components of T. aphylla were detected using standard techniques

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from the laboratory sheet. Animal models specified in conventional methods evaluatedthe percentage of granuloma tissue, inhibition percentage of edema, stabilizing abilityof membrane, and analgesic effectiveness. In addition, 100 mg/kg and 200 mg/kg doseregimens of T. aphylla considerably enhanced the reaction time and lowered the bodytemperature (p < 0.05) of rats compared to acetylsalicylic acid. Furthermore, the ethanolicextract of T. aphylla has shown membrane-stabilizing and analgesic properties [104].

5.8. Antidiabetic Activity

According to the WHO, 220 million humans are affected by diabetes; this number isanticipated to be double by 2030 [105]. However, glucose is an important energy source forthe cells that make up tissues and muscles, and it fuels the brain [106–108]. How the bodyuses glucose (blood sugar) is the cause of various diseases. The state of hyperglycemia iscalled diabetes mellitus [109]. This ailment hits the cardiovascular system, nervous system,kidneys, and eyes [110]. Inflammation is due to the triggering of various immune cellsleading to the death of pancreatic beta cells death via several inflammatory cytokines,thus resulting in insulin resistance [111]. Reactive oxygen species and oxidative stress aremajor causes of diabetes [112]. Diabetes is a severe metabolic condition that is treatedusing a variety of medicinal herbs in traditional medicine [113]. The main objective ofall diabetes care is to keep blood glucose levels stable. Traditional medicine and naturalproducts have the potential for developing therapeutics against chronic inflammatorydiseases. Many drugs are obtained from these herbs with limited adverse effects or noside-effects [64]. They are efficient herbal medications and natural antioxidants becausethey include antidiabetic chemicals, including alkaloids, phenolics, tannins, and flavonoids,reducing glucose absorption in the intestine or improving pancreatic tissue performance byboosting its performance in terms of insulin production [113]. This portion of the reviewaims to gather existing knowledge on T. aphylla regarding its antidiabetic potential withfuture research directions.

T. aphylla is used as a carminative, diuretic, and anti-inflammatory herbal remedy. Astudy was carried out to investigate the antihyperglycemic activity of T. aphylla leaves inSTZ-NIC-stimulated diabetes in Wistar Albino rats. T. aphylla’s methanol extract was exam-ined to determine its acute toxicity. Different doses (100 mg, 250 mg, and 400 mg/kg bodyweight per day) of T. aphylla leaves extract were administered for 21 days to diabetic Wistarrats. Multiple parameters were examined, such as hemoglobin, glycosylated hemoglobin,and fasting blood glucose levels. A total of 50 male Wistar rats, aged 8–10 weeks andweighing 220–320 g, participated in this examination. All rats stayed in an airy room with ahumidity of 40–50% and a temperature of 25 ± 2 ◦C in a 12 h light/dark cycle. For 2 weeksbefore the experiment and throughout the experiment, rats were fed regular laboratoryfood and had an available water supply. Rats were fasted for 12 h before receiving adiabetic injection. A single intraperitoneal (i.p.) injection of STZ (65 mg/kg body weight(b.w.)) freshly dissolved in ice-cold saline was used to induce diabetes [114]. An equalvolume of normal saline was injected into control animals. Nicotinamide (180 mg/kg,i.p.) was dissolved in normal saline and given 15 min before STZ administration [115].High pancreatic insulin release could be the cause of deadly hypoglycemia. At the end ofSTZ treatment over the next 24 h, a 10% glucose solution was fed to rats to subdue drugstimulated hypoglycemia [7]. In an acute toxicity investigation, animals given a methanolextract of T. aphylla showed no change in their behavior pattern [8]. Male Wistar micewere used in the experiment [116]. There was no evidence of death in the extract-treatedmice, and their performance looked to be normal. Up to the 1500 mg/kg dosage, nomortality or toxic response was observed until the end of the day. Blood glucose levelswere assessed in normal control and experimental animals on days 1, 3, 7, 14, and 21 of thetherapy. Compared to normal rats, STZ-NIC-stimulated diabetic rats exhibited a consid-erable rise in blood glucose levels. In the analysis of diabetic control, i.p. management ofT. aphylla (400 mg/kg body weight) substantially reduced FBS (fasting blood sugar). The21 days of therapy using T. aphylla were examined in terms of glycosylated hemoglobin

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and hemoglobin levels in usual and STZ-stimulated diabetic rats. Analysis of normalcontrol and diabetic rats showed a substantial drop in hemoglobin and a rise in HbA1c. Incontrast to diabetic control rats, i.p. T. aphylla improved hemoglobin and lowered HbA1c.Compared to the normal control rats, STZ treatment led to changes in HbA1c, hemoglobin,and blood glucose. The results showed that T. aphylla leaf extract lowers blood glucoselevels in people with diabetes. Furthermore, it can avoid diabetes complications caused byhigh blood glucose levels [8].

Antidiabetic properties are linked to the presence of terpenoids, flavonoids, coumarins,and a host of different secondary plant metabolites of T. aphylla [117]. Galls of T. aphyllacomprise polyphenols, such as gallic acid, ellagic acid, isoferulic acid, dehydrodigallic acid,and juglanin, as well as flavonoids such as isoquercitrin, quercetin glucoside, and its methylderivatives tamarixetin and tamarixin [4]. Gallic acid (GA) is a phytochemical with severalbiological functions, and it offers antioxidant and anti-advanced glycation properties. Italso inhibits angiotensin-converting enzyme [118]. Another study examined the combinedeffect of metformin with secondary metabolites such as gallic acid in improving antioxidantactivity and glucose metabolism in diabetic rats. The pancreas and liver of diabetic ratswere examined after administering metformin and GA. Outcomes showed that metforminand GA decreased the levels of IL-6 and TNF-α, and the expression of ATF4. Results ofthe study validated that the combination of GA and metformin is more effective thanmetformin alone [119]. Furthermore, another study validated that andrographolide andgallic acid synergistically reduce the level of blood glucose [120]. Therefore, GA meets thecriteria for being investigated as a therapeutic candidate in diabetic nephropathy, one ofthe most severe complications of diabetes. GA therapy significantly increased albumin andprotein levels while reducing plasma creatinine and blood urea nitrogen levels. GA alsoenhanced creatinine clearance. According to oxidative stress markers, GA treatment inmice exhibited significantly lessened oxidative stress in the kidney. In diabetic nephropathy,it also lowered TGF-β1 levels in the blood and renal tissue. According to the findings,T. aphylla is a good source of GA, which can be utilized successfully in treating diabeticnephropathy [118].

A flower extract of T. aphylla yielded tamarixetin 3,3′-disodium sulfate and glycosy-lated isoferulic acid [18]. An examination was carried out to determine the free-radicalscavenging and antiglycation properties of isoferulic acid (IFA). IFA’s free-radical scav-enging activity was calculated employing DPPH, FRAP, and metal adsorption assays.Various spectroscopic techniques were used to measure the antiglycation activity of IFA.The research outcomes displayed the effect of IFA on ROS and glycation via a structuraltransformation of HAS (human serum albumin). A comparison of the antioxidant proper-ties of IFA with GA, employing many biochemical and biophysical methods, showed thatIFA has ideal properties [121].

There is a constant rise in blood glucose in type 2 DM due to the breakdown of starchyfoods by glucose absorption and α-amylase in the small intestine by α-glucosidase [122].Suppression of α-glucosidase activity has been linked to a reduction in plasma glucoselevels and suppression of postprandial hyperglycemia. Consequently, it represents a suc-cessful remedial approach to treat type 2 DM by lowering glucose levels in the blood [123].In contrast, α-glucosidase blockers, such as voglibose, acarbose, and miglitol, lead togastrointestinal adverse effects such as diarrhea and flatulence. As a result, it is criticalto discover indigenous natural resources free of or with fewer adverse effects [124]. Astudy was carried out by Mahfoudhi et al. in which MeOH extracts from the leaves andstems of T. aphylla were examined to inhibit α-glucosidase actions. T. aphylla inhibitedα-glucosidase in a concentration-dependent manner, with 91.98% and 88.73% inhibitionat concentrations of 113.64 and 28.41 g/mL, respectively. In this study, IC50 values werefound for leaves (24.81 µg/mL) and stem (8.41 µg/mL). These results were lower thanthose reported for acarbose (IC50 = 300 g/mL), the positive control. The inhibition byT. aphylla extracts was significantly higher compared to other botanicals employed in dia-betic medication, such as Glycyrrhiza uralensis (IC50 = 20.1 mg/mL) [125] and Viscum album

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(IC50 = 11.7 mg/mL) [54,126]. It has been reported in previous studies that quercetin, el-lagic acid, and kaempferol inhibited α-glucosidase [127,128]. Therefore, it can be concludedthat T. aphylla’s MeOH extracts exhibited higher antidiabetic properties due to the presenceof quercetin, ellagic acid, and kaempferol. It can also be concluded that α-glucosidasedisplays suppressive properties, whereas T. aphylla exhibits antioxidant properties. As aresult, T. aphylla might be beneficial in the therapy of DM. Furthermore, T. aphylla worksby blocking a pathology-related enzyme and strengthening the patients’ antiradical de-fenses [54]. The proposed mechanism underlying the glucosidase-inhibitory properties ofT. aphylla is shown in Figure 6.

Separating the active components of T. aphylla and the molecular interactions of itsconstituents for investigation of their therapeutic effects requires more research. As aresult, we must keep looking for new and, if possible, more effective antidiabetic propertiesof T. aphylla, and its vast reservoirs of phytoconstituents might represent an excellentalternative. Despite this, there is little research on the plant’s antidiabetic properties.


Figure 6. The proposed mechanism underlying the glucosidase-inhibitory properties of T. aphylla.

Separating the active components of T. aphylla and the molecular interactions of its constituents for investigation of their therapeutic effects requires more research. As a re-sult, we must keep looking for new and, if possible, more effective antidiabetic properties of T. aphylla, and its vast reservoirs of phytoconstituents might represent an excellent al-ternative. Despite this, there is little research on the plant’s antidiabetic properties.

5.9. Cytotoxic Activity Natural materials have been recognized as possible sources of human medicines

since ancient times. Over 50% of all pharmaceutical drugs are still natural ingredients [129,130]. Currently, natural sources such as plants, microorganisms, and sea creatures account for more than 60% of commercially accessible anticancer medicines [131–134]. A total of 3000 plant species have been utilized to treat various kinds of cancer [132,135]. Every year, many chemical entities are introduced to the market or undergo clinical stud-ies [129]. Plant bioactive compounds and phytochemicals can prevent more than 20% of cancer diagnoses and 200,000 cancer-related deaths per year. Several plants are being studied for cancer prevention due to their lesser toxicity, safety, and antioxidant qualities [80,132,136]. Since the 1940s, natural products or derivatives of natural products have ac-counted for 48.6% of the 175 small compounds authorized for cancer treatment [137]. Therefore, it is essential to obtain valuable and harmless unique agents with cytotoxic properties with minimal or no adverse effects on normal cells, along with extraordinary potency at various sites, as well as low cost and acceptance in the community. Conse-quently, conducting various in vitro, in vivo, and clinical examinations is also necessary [138].

It is essential to test cytotoxicity to establish the safety profile of T. aphylla and obtain active constituents [139]. To investigate the cytotoxic impact, fresh and disease-free leaves of T. aphylla were collected from several geographical sites in Saudi Arabia. In vitro, the anticancer and cytotoxic effects of T. aphylla leaves were examined, employing MCF

Figure 6. The proposed mechanism underlying the glucosidase-inhibitory properties of T. aphylla.

5.9. Cytotoxic Activity

Natural materials have been recognized as possible sources of human medicines sinceancient times. Over 50% of all pharmaceutical drugs are still natural ingredients [129,130].Currently, natural sources such as plants, microorganisms, and sea creatures account formore than 60% of commercially accessible anticancer medicines [131–134]. A total of3000 plant species have been utilized to treat various kinds of cancer [132,135]. Every year,many chemical entities are introduced to the market or undergo clinical studies [129]. Plantbioactive compounds and phytochemicals can prevent more than 20% of cancer diagnosesand 200,000 cancer-related deaths per year. Several plants are being studied for cancerprevention due to their lesser toxicity, safety, and antioxidant qualities [80,132,136]. Sincethe 1940s, natural products or derivatives of natural products have accounted for 48.6% of

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the 175 small compounds authorized for cancer treatment [137]. Therefore, it is essential toobtain valuable and harmless unique agents with cytotoxic properties with minimal or noadverse effects on normal cells, along with extraordinary potency at various sites, as wellas low cost and acceptance in the community. Consequently, conducting various in vitro,in vivo, and clinical examinations is also necessary [138].

It is essential to test cytotoxicity to establish the safety profile of T. aphylla and obtainactive constituents [139]. To investigate the cytotoxic impact, fresh and disease-free leavesof T. aphylla were collected from several geographical sites in Saudi Arabia. In vitro, theanticancer and cytotoxic effects of T. aphylla leaves were examined, employing MCF (breastadenocarcinoma cells) as carcinoma cells and Vero cells as normal cells. The 50% cytotoxicityconcentration denoting the concentration leading to a 50% reduction in cell viability wasinvestigated. The result of the MTC colorimetric test was determined to be 2000 g/mL. Amild cytotoxic effect was observed at high concentrations of leaf extract of T. aphylla onthe Vero cell line with a 50% cytotoxicity concentration >100 g/mL. In a concentration-dependent manner, the methanolic extract inhibited MCF cancer cells. The findings of thecytotoxicity test of T. aphylla leaf methanolic extracts on Vero cells indicated that this plant ispotentially nontoxic. As a result, the findings of this investigation suggested that T. aphylla’scytotoxic strength should be considered a potential applicant for future testing in vivo andin vitro against various additional cell types. This is in line with earlier research on theintriguing anticancer properties of Tamarix species [80]. Antiproliferative effectiveness wasfound against MCF-7 cells using the leaf extract of T. aphylla; thus, it should be employedin future antiproliferative studies. GC–MS and GC methods were used to examine theantiproliferative activity of the essential oil composition of aerial parts of T. aphylla aqueousextract (AE) and ethanol extract (EE), as well as to investigate potential cytotoxicity againstpancreatic carcinoma, colorectal adenocarcinoma, human breast adenocarcinoma (MCF-7),and normal human fibroblasts. It was found in the GC–MS analysis of T. aphylla EO thatthe principal component was 6,10,14-trimethyl-2-pentadecanone in terms of predominanceand richness among non-terpenoid nonaromatic hydrocarbons (52.39%). Biological resultsshowed that T. aphylla extracts exhibit cytotoxicity in a dose-dependent manner againstmost tested cell lines. Nevertheless, potent effects were recorded against MCF-7 cells withIC50 values of 2.17 ± 0.10 and 26.65 ± 3.09 µg/mL for T. aphylla EE and AE, respectively.T. aphylla AE has exhibited a comparable cytotoxic profile to control drug cisplatin (IC50value of 1.17 ± 0.13 µg/mL), along with a complete safety profile against normal fibroblastcells (IC50 of T. aphylla AE versus cisplatin: 79.99 ± 4.90 versus 9.08 ± 0.29 µg/mL).In addition, at concentrations less than 30 g/mL, the AE showed no antiproliferativepotential against Panc-1 or Caco-2 cancer cell lines. This study concluded that T. aphyllaextracts might be cytotoxic agents with selective cytotoxicity profiles and high safety [140].Another study used the brine shrimp method to examine the cytotoxic property of methanolextracts of T. aphylla leaves. This method showed a 70% mortality rate to T. aphylla extractat a 500 µg/mL concentration [141]. The cytotoxic potential of T. aphylla bark extractagainst human erythrocytes was assessed. T. aphylla bark extract exhibited 3.48 ± 1.08hemolytic activity compared to the positive control. The studied T. aphylla extracts had alower hemolytic potential, making them safe in pharmaceutical applications [142]. Manystudies reported a high content of polyphenols, tannins, and flavonoids [143–145]. Variousphenolic compounds isolated from Tamaricaceae were tested against different cancercell lines for their cytotoxic effects [146]. Tamarixetin was discovered to be cytotoxic toleukemia cells [147]. In a time- and dose-dependent manner, this compound suppressedproliferation, caused apoptosis, and stopped cell-cycle progression [148]. Ellagitanninshave also exhibited anticancer and antiangiogenic properties mediated by the host [149].As shown by TLC tests, secondary metabolites and phenolic fractions may account forthe higher cytotoxic property found in various studies of the extracts of T. aphylla [140].T. aphylla extracts have shown antiproliferative activities against MCF-7 cancer cell lines,which could be the basis to attract future research to develop novel cancer therapies.The reported analgesic activity mechanism, anticholinesterase action, cytotoxicity against

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different cell lines, and antifungal activity against different fungal strains of T. aphylla areshown in Figure 7.


Figure 7. Analgesic, anticholinesterase, cytotoxicity, and antifungal activity of T. aphylla.

6. Toxicity Natural medicinal plants are important because they are rich in diverse phytochem-

ical components. In addition to being extensively accessible and commercially useful, these phytochemical substances have pharmacological effects in treating various medical situations. Plant phytochemical substances have been investigated in numerous experi-ments to discover the molecular basis of their interaction with medicines and illnesses [150]. However, plants are potentially toxic due to their chemical components; as a result, certain plants employed in traditional medicine are intrinsically harmful [151–153]. T. aphylla (L. Karst) methanol extract was examined for acute toxicity. In the three test groups, a leaf extract of T. aphylla was administered intraperitoneally with doses of 100 mg, 250 mg, and 400 mg/kg body weight to the mice of every group per day. The control group was administered saline; mice were examined in terms of the following factors for 2 h: (a) behavioral determinants: agitation, alertness, dread, and irritability; (b) neurolog-ical determinants: reaction, impulsive action, touch reaction, gait, and pain response; (c) autonomic determinants: urination and excretion. They were monitored for mortality or lethality after 24 h. In an acute toxicity investigation, the methanol extract of T. aphylla-treated mice did not lead to changes in behavioral pattern. Male Wistar mice were used in the experiment. There was no evidence of death in the extract-treated mice, and their performance looked to be normal. No toxicity or mortality was observed at the end of the day after administering 1500 mg/kg; therefore, T. aphylla’s extracts are nontoxic [8]. The results of another toxicological study on T. phylla extract at various doses up to 2000 mg/kg did not show any adverse effect [70]. Another study of T. aphylla extract showed a protec-tive effect against DOX cardiotoxicity [154]. Toxicity was negligible in T. aphylla from Saudi Arabia and Pakistan [144]. Table 3 presents the results of various preclinical studies.

Figure 7. Analgesic, anticholinesterase, cytotoxicity, and antifungal activity of T. aphylla.

6. Toxicity

Natural medicinal plants are important because they are rich in diverse phytochemicalcomponents. In addition to being extensively accessible and commercially useful, thesephytochemical substances have pharmacological effects in treating various medical situa-tions. Plant phytochemical substances have been investigated in numerous experiments todiscover the molecular basis of their interaction with medicines and illnesses [150]. How-ever, plants are potentially toxic due to their chemical components; as a result, certain plantsemployed in traditional medicine are intrinsically harmful [151–153]. T. aphylla (L. Karst)methanol extract was examined for acute toxicity. In the three test groups, a leaf extract ofT. aphylla was administered intraperitoneally with doses of 100 mg, 250 mg, and 400 mg/kgbody weight to the mice of every group per day. The control group was administered saline;mice were examined in terms of the following factors for 2 h: (a) behavioral determinants:agitation, alertness, dread, and irritability; (b) neurological determinants: reaction, impul-sive action, touch reaction, gait, and pain response; (c) autonomic determinants: urinationand excretion. They were monitored for mortality or lethality after 24 h. In an acute toxicityinvestigation, the methanol extract of T. aphylla-treated mice did not lead to changes inbehavioral pattern. Male Wistar mice were used in the experiment. There was no evidenceof death in the extract-treated mice, and their performance looked to be normal. No toxicityor mortality was observed at the end of the day after administering 1500 mg/kg; therefore,T. aphylla’s extracts are nontoxic [8]. The results of another toxicological study on T. phyllaextract at various doses up to 2000 mg/kg did not show any adverse effect [70]. Anotherstudy of T. aphylla extract showed a protective effect against DOX cardiotoxicity [154].Toxicity was negligible in T. aphylla from Saudi Arabia and Pakistan [144]. Table 3 presentsthe results of various preclinical studies.

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Table 3. Characteristics of included preclinical studies.

Pharmacological Activity Plant Part Solvent for Extraction Model/Induction/Agent/Species Dosage or Concentration Sample Size/Pathogens Results References

Antidiabetic Leaf MeOHIn vivo study, diabetic Wistar

rats (induced bynicotinamide + STZ)

100, 250, 400 mg/kg/day 50 male Wistar rats Outcomes showed nontoxic and

antidiabetic properties [8]

Antidiabetic Leaf, stem MeOH In vitro study,α-glucosidase inhibitory assay 1–1000 µg/mL - Antidiabetic properties were shown [54]

Antipyretic, analgesic, andanti-inflammatory

propertiesAerial parts Aqueous ethanolic extract

In vivo,edema and yeast-induced,

carrageenan-inducedpaw edema

100 mg/kg/daySwiss albino male mice

(20–30 g), three groups ofsix mice

Outcomes revealed antipyretic andanalgesic activities with lessened

anti-inflammatory action[21]

Anti-inflammatory andwound healing Leaf EtOH

In vivo,carrageenan-induced

paw edema15%, 25% in gel base Wistar rats (180–200 g) Outcomes showed gel usefulness [70]

Antimicrobial Leaf, stem,bark Diverse extracts

In vitro study, micro-titerassay, agar well

diffusion method1 mg/mL - Helpful against 11 biofilm-forming

strains [27]

Leaf MeOH extract

In vitro:antibacterial

activity againstEscherichia coli and

Staphylococcus aureus,agar dilution

method againstthree Aspergillus species

0.86–30 mg/ mL - No considerable antibacterial effect [141]

Antifungal Leaf MeOH extract In vitro: dilution of agar tubes 67 µL (200 µg/mL) -

T. aphyllashowed significant

antifungal activity: 70%, 55%, and54% against Aspergillus flavius,

Aspergillus niger, and Aspergillusfumigatus, respectively

[141]

Stem,bark Crude ethanolic extracts In vitro Concentrations 500 ppm,

1000 ppm, and 2000 ppm Six pathogenic fungi Maximum inhibition has beenshown by T. aphylla [90]

Bark MeOH In vitro: disc diffusion assay 25, 50, 75, and 100 mg/mL Aspergillus flavus andCandida albicans

T. aphylla inhibited most fungalstrains at higher concentrations [81]

Toxicity Leaf MeOH In vivo,toxicity study in mice 500–2100 mg/kg/day 50 male, Wistar rats

(220–320) g Nontoxic [8]

Toxicity Leaf EtOH In vivo,toxicity study in rats

Doses administered: 50,100, 300, 1000, and 2000

mg/kg body weightWistar rats No toxicity was reported up to 2000

mg/kg body weight [70]

Toxicity Leaf MeOH In vivo 50–500 mg/ mL Brine shrimp Brine shrimp showed a 70%mortality rate [141]

Wound healing Leaf EtOHIn vivo,

excision wound and inducedpaw edema model

15%, 25% in gel base Wistar rats T. aphylla leaf extract possesseswound-healing properties [70]

Periodontal disease Bark, stem, leaves Methanol, ethanol, acetone,and water extracts In vitro, phylogenetic analysis - Pathogenic bacteria from

dental biofilms.T. aphylla showed potent

antibiofilm activity [27]

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7. Concluding Remarks

This review covered the recent literature related to the ethnobotanical uses, phyto-chemical compounds, pharmacological effects, and toxicology of T. aphylla. The findingsof this work establish the connection between T. aphylla in the traditional medication sys-tem and its impact on other biological properties such as antibacterial, anti-inflammatory,antidiabetic, analgesic, wound healing, antifungal, and anticholinesterase activities. Theleaves and stem/bark seem to be the most effective plant parts of T. aphylla as these partsshowed several therapeutic activities. However, there is a need to study the isolation andcharacterization of phytoconstituents, as well as the molecular mechanism of componentsfrom these plant parts of T. aphylla. Different chemical compounds such as polyphenols,flavonoids, and tannins account for the various biological activities of T. aphylla. Isola-tion of secondary metabolites and their examinations in vitro and in vivo to test variouspharmacological activities could attract future research and drug discovery.

However, nonclinical studies have shown that the T. aphylla has significant antimicro-bial, antioxidant, and cytotoxic activities. Thus, more extraction, isolation, and purificationstudies are needed to develop potential drugs to treat various ailments. The findings ofmany studies exhibited that the leaf extract of T. aphylla is nontoxic with no reported mor-tality, while toxicity of T. aphylla was found to be negligible in studies from Saudi Arabiaand Pakistan. The pharmacological properties of T. aphylla, according to study findings,support its traditional applications. Clinical trials establishing the health benefits were notfound; therefore, high-quality preclinical studies and well-designed clinical studies areneeded to confirm the efficacy and safety of T. aphylla in people.

Moreover, herbal supplements have not received the same scientific scrutiny and arenot as strictly regulated as medications. Natural products are regulated by the US Foodand Drug Administration (FDA), but not as strictly as prescription or over-the-counter(OTC) drugs. Natural products should be free of contaminants and must meet specificquality standards. Some herbs can cause serious side-effects when mixed with aspirin,blood thinners, and blood pressure medications. Many herbal supplements can affect thesuccess of surgery. Some may decrease the effectiveness of anesthesia or cause dangerouscomplications, such as bleeding. Few natural products have been tested in children or haveestablished safe doses. Moreover, older adults may metabolize medications differently.Therefore, it is essential to learn about the potential benefits and side-effects of herbalsupplements before they are prescribed in the clinic.

Author Contributions: Conceptualization and methodology, S.W., S.A.A. and S.S.A.; writing—originaldraft preparation, S.W., S.S.A., G.D., U.H., W.A. and M.A.; writing—review and editing, S.W., S.A.A.,A.A., G.K. and R.V. All authors have read and agreed to the published version of the manuscript.

Funding: Please add: This research was funded by Deanship of Scientific Research, King Khalid Uni-versity, Abha, Saudi Arabia, through the small Research Group Program grant number RGP.1/336/42.

Acknowledgments: The authors extend their appreciation to the Deanship of Scientific Research atKing Khalid University, Abha, Saudi Arabia for funding this work through the Small Research GroupProject under grant number RGP.1/336/42.

Conflicts of Interest: The authors declare no conflict of interest.

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Pharmacological Efficacy of Tamarix aphylla - MDPI

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